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"conduction"
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Progressive Conduction System Disease in Hydroxychloroquine Cardiotoxicity: A Call for Early Vigilance
Hydroxychloroquine (HCQ) cardiotoxicity is increasingly recognized, yet progressive conduction system disease remains underappreciated and may represent a lethal phenotype. We report a 67-year-old female on chronic HCQ who developed progressive conduction abnormalities culminating in cardiogenic shock and sudden death despite initial stabilization with isolated atrial pacing. Autopsy revealed extensive sinoatrial and atrioventricular nodal lysosomal toxicity and fibrosis confirming irreversible conduction injury. This case highlights the lysosomal basis of HCQ toxicity and reframes conduction disease as a primary, irreversible manifestation. Vigilant ECG surveillance and early consideration of dual-chamber pacing may prevent catastrophic outcomes in patients on chronic HCQ therapy.
Journal Article
Knitted, textile, high impedance surface with integrated conducting vias
This paper presents an experimental, microwave high impedance surface (HIS) manufactured from a combination of both conducting and insulating yarns using commercial, computerised flat-bed knitting machines. The HIS consists of a knitted, conducting ground plane, a polyester spacer layer and a knitted, conducting patterned top surface. The structure also contains vias that link the conducting elements of the top layer to the ground plane. The entire structure, including the vias, is knitted in one continuous process that is both low cost and highly efficient in terms of manufacturing time. The measurements of the surface wave transmission properties of the knitted, textile HIS are made and data are presented that show that the HIS prevents surface wave transmission over a band of frequencies between 4 and 5GHz.
Journal Article
Decoupling thermal stability and insulation in dielectric polymers via donor-acceptor rearrangement
Polymer dielectrics with enhanced thermal stability and electrical insulation are urgently needed for capacitive energy storage applications in electric power systems. There is a persistent challenge to break the contradictory correlation between high heat resistance and low electrical conduction in polymers. Here, we employ benzyl-induced crosslinking to rearrange short-range structural units in polyimide chains, reducing electrical conduction loss. The designed polymer exhibits an electrical conductivity more than 3 orders of magnitude lower than that of commercial heat-resistant polymers, while its glass transition temperature (
T
g
) increases from 236.31 °C (for polyetherimide) to 289.72 °C. Consequently, a discharged energy densities of 6.38 J cm
−3
and 3.04 J cm
−3
, with charge-discharge efficiencies above 90%, are achieved at 200 °C and 250 °C, respectively, demonstrating among the best in all-organic dielectric polymers. This work presents a feasible approach to break the adverse correlation between thermal stability and electrical insulation in polyimide materials.
Polymer dielectrics have potential in capacitive energy storage applications, but achieving the required thermal stability and electrical insultation is challenging. Here, the authors report a method to rearrange short-range structural units within polyimide chains to give improved properties.
Journal Article
Cardiac radiotherapy induces electrical conduction reprogramming in the absence of transmural fibrosis
Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in Na
V
1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to Na
V
1.5 upregulation after RT. Clinically, RT was associated with increased Na
V
1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.
Noninvasive cardiac radiotherapy may effectively manage ventricular tachycardia in refractory patients, but its radiobiologic mechanisms of action are unclear. Here, the authors show that photon radiation durably and favourably reprograms cardiac conduction in the absence of transmural fibrosis suggesting this could be the mechanism through which cardiac radiotherapy to modulates arrhythmia susceptibility.
Journal Article
Self-sustainable protonic ceramic electrochemical cells using a triple conducting electrode for hydrogen and power production
The protonic ceramic electrochemical cell (PCEC) is an emerging and attractive technology that converts energy between power and hydrogen using solid oxide proton conductors at intermediate temperatures. To achieve efficient electrochemical hydrogen and power production with stable operation, highly robust and durable electrodes are urgently desired to facilitate water oxidation and oxygen reduction reactions, which are the critical steps for both electrolysis and fuel cell operation, especially at reduced temperatures. In this study, a triple conducting oxide of PrNi
0.5
Co
0.5
O
3-δ
perovskite is developed as an oxygen electrode, presenting superior electrochemical performance at 400~600 °C. More importantly, the self-sustainable and reversible operation is successfully demonstrated by converting the generated hydrogen in electrolysis mode to electricity without any hydrogen addition. The excellent electrocatalytic activity is attributed to the considerable proton conduction, as confirmed by hydrogen permeation experiment, remarkable hydration behavior and computations.
While producing renewable fuel is crucial for a sustainable energy economy, there is still a need for active and durable materials capable of efficient fuel generation and utilization. Here, authors demonstrate a triple-conductive oxide as an oxygen electrode for H
2
or electricity production.
Journal Article
Spatially resolved multiomics of human cardiac niches
The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system
1
. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated
FOXP2
in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug–target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG
+
and IgA
+
plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.
Single-cell and spatial transcriptomic analysis of eight human heart tissues reveals the cellular profiles and tissue architecture of niches including the cardiac conduction system, and a new tool, drug2cell, identifies drug target expression.
Journal Article
Rationale and design of a randomized clinical trial comparing safety and efficacy of myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: The LANDMARK trial
The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis.
The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020–000,137–40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 1:1 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety and efficacy endpoint is a composite of all-cause mortality, all stroke (disabling and nondisabling), bleeding (life-threatening or disabling), acute kidney injury (stage 2 or 3), major vascular complications, prosthetic valve regurgitation (moderate or severe), and conduction system disturbances (requiring new permanent pacemaker implantation), according to the Valve Academic Research Consortium-2 criteria at 30-day follow-up. All patients will have follow-up to 10 years following TAVR.
The LANDMARK trial is the first randomized head-to-head trial comparing Myval THV series to commercially available THVs in patients indicated for TAVR. We review prior data on head-to-head comparisons of TAVR devices and describe the rationale and design of the LANDMARK trial.
Journal Article
Electrodiagnostic subtyping in Guillain–Barré syndrome patients in the International Guillain–Barré Outcome Study
Background and purpose Various electrodiagnostic criteria have been developed in Guillain–Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. Methods From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. Results Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. Conclusions and discussion This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.
Journal Article